Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism
Bibliographic record
Abstract
The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 individuals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in individuals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".